Disease relevance of Bx

• We isolated recombinant lambda phage clones spanning 49 kilobases of DNA which contain the Beadex and heldup-a loci of Drosophila melanogaster [1].

High impact information on Bx

• Here we report that transgenic expression of a dominant-active Drosophila Rho guanosine triphosphatase, Drac1, rescued photoreceptor morphogenesis in rhodopsin-null mutants; expression of dominant-negative Drac1 resulted in a phenotype similar to that seen in rhodopsin-null mutants [2].
• Beadex encodes an LMO protein that regulates Apterous LIM-homeodomain activity in Drosophila wing development: a model for LMO oncogene function [3].
• Phosphorylation by mitogen-activated protein kinases and interaction with Rho GTPases have been proposed as regulatory mechanisms [4].
• Increasing evidence suggests that the Rho GTPases and their upstream positive regulators, guanine nucleotide exchange factors (GEFs), also play important roles in the control of growth cone guidance in the developing nervous system (Luo, L. 2000. Nat. Rev. Neurosci. 1:173-180; Dickson, B.J. 2001. Curr. Opin. Neurobiol. 11:103-110) [5].
• Nineteen of the Drosophila DNA fragments cloned correspond to one locus, termed Clone A, which is 312 bp in length and contains five vnd/NK-2 homeodomain core consensus binding sites, 5'-AAGTG, and is part of the first intron of the Beadex gene [6].

Biological context of Bx

• This provides molecular grounds for the suppression of the Bx phenotype by hdp-a mutations [7].
• Thus, since rhombotin lacks a DNA-binding homeodomain, this protein might belong to a new class of transcriptional regulators which modulate transcription via intermolecular competitive binding to the LIM domains of certain DNA-binding transcription factors [8].
• Consistent with a role for Lmo in LN(v)function,Lmomutants also show defects in circadian rhythms of behavior [9].
• In this mutant, deletion of sequences no more than 1,600 base pairs from the Beadex locus accompanies the loss of heldup-a function [1].
• The Rho-kinases are widely utilized downstream targets of the activated Rho GTPase that have been directly implicated in many aspects of Rho-dependent effects on F-actin assembly, acto-myosin contractility, and microtubule stability, and consequently play an essential role in regulating cell shape, migration, polarity, and division [10].

Anatomical context of Bx

• Previous work has shown that Cdc42 and Rac promote neurite outgrowth by a pathway that is antagonistic to Rho [11].
• The small GTPase Rho is a molecular switch that is best known for its role in regulating the actomyosin cytoskeleton [12].
• In the posterior spiracles of the fly embryo, this asymmetric activation is achieved by at least two mechanisms: the apical enrichment of Rho1; and the opposing distribution of Rho activators and inhibitors to distinct compartments of the cell membrane [13].
• In the paradigm emerging from cultured fibroblasts, nonmuscle actomyosin-II contractility, mediated by the small GTPase Rho, is required to cluster integrins at focal adhesions [14].
• The Beadex locus was highly mutable in these hybrids but did not mutate at all in the sample of gametes from the M X Q hybrids [15].

Associations of Bx with chemical compounds

• We propose that Lmo controls the responsiveness of LN(v)s to cocaine, which in turn regulate the flies' behavioral sensitivity to the drug [9].
• The Drosophila-expressed Rho associated with the 3-hydroxyretinal chromophore but failed to evoke an electroretinogram response from fly photoreceptors [16].

Other interactions of Bx

• We report the cloning of a LIM-containing gene from Drosophila, termed Dlmo, which is highly homologous to the vertebrate LIM-only (LMO) genes [7].
• The 3' untranslated (UTR) of Dlmo contains multiple motifs implicated in negative post-transcriptional regulation, including AT-rich elements and Brd-like boxes [7].
• CONCLUSIONS: In the light of our findings, we conclude that Rho GTPases/JNK cascades are not major effectors of planar polarity in the Drosophila eye [17].
• Expression of Lmo in the principal Drosophila circadian pacemaker cells, the PDF-expressing ventral lateral neurons (LN(v)s), is sufficient to confer normal cocaine sensitivity [9].
• Furthermore, Minute mutations that reduce the efficiency of protein synthesis and extend developmental time allow Beadex -related cell death to be compensated for by additional cell replacement or increased cell lifespan [18].

References